Background:  Anemia is associated with poorer survival in HIV-positive patients in industrialized countries. Severe anemia occurs in 2 to 4% patients initiating zidovudine (ZDV)-based therapy, but little is known about incidence and risk factors in resource-limited countries.

Methods:  DART is a randomized trial of monitoring strategies and planned treatment interruptions (after 24 weeks) in 3300 symptomatic ART-naive adults with CD4 count < 200 cells/mm³ from 3 sites (2 Uganda, 1 Zimbabwe). The first-line regimen is combivir plus either tenofovir DF, nevirapine, or abacavir. Full blood counts are performed at baseline, weeks 4 and 12, then every 12 weeks, and also if clinically indicated. We analyzed the prevalence of anemia at scheduled assessments, and considered sex, age, and baseline laboratory measurements as potential risk factors for ever developing grade 4 anemia (< 6.5 mg/dL) at any time-point using logistic regression in a global analysis (not by randomized groups).

Results:  To July 2004, 2932 adults had been randomized (65% women; median age 37 years; 23% WHO stage 4; median baseline CD4 86), and median follow-up was 24 weeks (IQR 12 to 36). Of 2854 patients with baseline haemoglobin, 340 (12%) already had anaemia (Hb < 9.5 mg/dL), with 7 (0.2%) having grade 2 toxicity or higher (Hb < 8 mg/dL, a minor protocol violation). Following ART initiation, 610 (21%) patients developed a new episode of anemia (worsening, or new episode following resolution), and 161 (5.5%) developed new grade 4 anemia (12 having repeated distinct grade 4 episodes). The first grade 4 episode was identified a median of 12 weeks after ART initiation (IQR 8 to 17, range 2 to 40). Correspondingly, the prevalence of grade 4 anemia was 0.6%, 2.2%, 0.7%, 0.4%, and 0.3% at 4, 12, 24, 36, and 48 weeks, respectively. Based on concurrent MCV, 37% grade 4 anemias were microcytic, 27% normocytic, and 21% macrocytic (15% had no MCV). Women, and those with lower hemoglobin, lower CD4 count, and lower weight at baseline were all significantly more likely to develop grade 4 anemia (all p < 0.05). Baseline neutrophil count was not an additional predictor.

Conclusions:  Although the incidence of grade 4 anemia in DART is higher than expected, this may be partly explained by a higher proportion of women, more advanced disease, and lower hemoglobin at baseline in DART compared to studies in industrialised countries, as well as greater risk of malaria.

Keywords: Anaemia; Zidovudine; Africa